The present disclosure relates to a delivery device and storage system for controlled administration of mother's colostrum and milk oropharyngeally to neonates, inclusive of any of the following: extremely low gestational age neonates (ELGANS: GA<28 weeks), extremely low birth weight (ELBW: BW<1000 g) infants, very low birth weight (VLBW: BW<1500 g) infants, low birth weight (LBW: BW<2500 g) infants, premature (GA<37 weeks) infants, or other “at risk” term infants. Although the delivery device and storage system for oropharyngeal administration of mother's colostrum and milk is designed for use with any neonate, the infants that would derive the most benefit are premature infants, particularly those that are VLBW; weighing less than 1500 grams at birth.
Worldwide, up to 18 million infants are born prematurely.1, 2 Of these infants, 84% are born between 32 and 36 weeks gestational age (GA), 10% are born between 28 and 32 weeks GA, and 5% are born at less than 28 weeks GA.1, 2 In the United States, approximately 550,000 infants are born premature (GA<37 weeks) annually3, 4 This represents one out of every 8 infants born in the U.S. The incidence of preterm birth has increased significantly since 1990, as a result of reproductive technologies. Survival of extremely premature infants has also increased dramatically in recent decades as a result of advances in neonatal medicine and technology. Recent data shows that >85% of VLBW infants born in the United States will survive to discharge.5, 6 Very low birth weight (VLBW: BW<1500 g) infants represent only 1.5% of all lives births in the United States,7 yet account for approximately $13.4 billion annually; 30% of total newborn healthcare costs in the U.S.8-10; largely as a result of infectious morbidities. The smallest of the VLBW infants are born before the last trimester of pregnancy. These immunodeficient infants sustain long hospitalizations (up to 4 months) in the pathogen-laden neonatal intensive care unit (NICU), while requiring numerous invasive devices for the provision of life-saving therapies. These factors place them at high risk for acquiring several episodes of device-associated healthcare-associated infections (DA-HAIs), including blood-stream infection and ventilator-associated pneumonia (VAP), during their prolonged NICU stay.11 Necrotizing enterocolitis (NEC), while not a DA-HAI, is another potentially lethal (gastrointestinal) infectious and inflammatory disorder for the VLBW infant. The mortality associated with blood-stream infection, ventilator-associated pneumonia, and necrotizing enterocolitis is high (10-49%)12 for these extremely premature infants. Survivors suffer from long-term handicapping morbidities, including severe neurological impairments which create a massive financial burden for families, healthcare systems, educational systems, and society. A 25% reduction in the incidence of blood-stream infection for extremely premature VLBW infants could yield a saving of 24 million dollars annually.13 The total additional hospital costs associated with necrotizing enterocolitis have been estimated to be 6.5 million per year. Prevention of a single case of surgical necrotizing enterocolitis could reduce the financial burden of prematurity in the U.S. at an approximate savings of $125,000 per case; conservatively.14, 15 While the complete elimination of blood-stream infection, ventilator-associated pneumonia and necrotizing enterocolitis is not possible with the increased survival of extremely premature infants, and the high incidence of device utilization in the NICU, even a modest reduction in the incidence of these infections could yield a substantial cost savings in health dollars, and improved health outcomes for these vulnerable infants. The development of safe, cost-effective, and efficacious preventative strategies, including adjunctive immunologic interventions is an urgent priority.16 
Own mother's milk (OMM) feedings have been consistently linked with a lower incidence of infections for preterm infants.17-21 This protection is attributed to a multitude of milk biofactors which provide passive immune protection, modulate the infant's mucosal and systemic immune responses, and promote intestinal maturation. The milk expressed by women who deliver extremely premature infants is more highly concentrated in protective (immune and trophic) biofactors, (also present in amniotic fluid), compared to the milk expressed by women who deliver at term. These gestation-specific trends in composition are especially pronounced in early milk (colostrum) which suggests an important biological function for protecting the extremely premature infant from infection during the first weeks of life and facilitating extra-uterine transition.22 
Mother's milk is administered to extremely premature infants (i.e. ELBW, ELGANs, VLBW) as an enteral “feeding” via a nasogastric tube. However, clinical instability precludes enteral feedings for extremely premature infants in the first 2 weeks of life. This post-birth fasting leads to intestinal atrophy and abnormal intestinal colonization which increases the risk for feeding intolerance, blood-stream infection and necrotizing enterocolitis. Once feedings are started, extremely premature infants typically require many weeks to reach full enteral feedings (150 mL/kg/day) because the immature gastrointestinal tract makes tolerating feedings problematic. The prolonged time to reach full enteral feedings necessitates the long-term placement of central venous catheters for the administration of parenteral nutrition; significantly increasing the risk for acquiring blood-stream infection and necrotizing enterocolitis. Because enteral feedings are given via a nasogastric tube for many weeks, stimulation of the infant's oropharyngeal-associated lymphoid tissue (OFALT) by protective (immune and trophic) biofactors in mother's milk, cannot occur until the infant is developmentally ready to begin “per oral” feeds at 32 weeks post-conception. Therefore, for up to 9 weeks post-birth (for infants born as early as 23 weeks gestation) the infant's oropharynx is not exposed to protective biofactors because enteral feedings are given via a nasogastric tube which bypasses the oropharynx. In a normal term pregnancy, in-utero stimulation of the oropharynx is provided until 40 weeks gestation by protective immune and trophic biofactors present in amniotic fluid.23 With a preterm delivery however, amniotic fluid exposure stops abruptly and with our current standard of care, OFALT stimulation is delayed for up to 2 months for extremely premature infants. Importantly, if formula (and not mother's milk) is used for per oral feedings, then the infant's OFALT will never again be exposed (post-birth) to immune and trophic biofactors. The delayed (or absent) exposure post-birth to protective milk biofactors is a critical barrier to optimizing outcomes for extremely premature infants, and a clinical dilemma for NICU's not only in the United States, but world-wide. The immune and trophic benefits of mother's milk underscore the urgent need to test strategies to facilitate early exposure to milk biofactors, even when the infant cannot be fed. Oropharyngeal administration of mother's colostrum and milk is an innovative intervention that has been recently introduced clinically, however the proper delivery device and storage system for this intervention is not yet available to clinicians who care for high-risk infants in the NICU.
Oropharyngeally-administered mother's colostrum and milk can be utilized as an adjunct immunological intervention to protect recipient infants against infections, including blood-stream infection, ventilator-associated pneumonia, and necrotizing enterocolitis. During oropharyngeal administration,22 small drops of milk are placed directly onto the oral mucosa, followed by gentle buccal swabbing to evenly distribute the milk. Oropharyngeally-administered mother's milk with buccal swabbing may protect the recipient infant against infection via (1) cytokine interaction with immune cells within OFALT (2) passive mucosal absorption of protective immune and trophic factors such as lactoferrin and epidermal growth factor, and (3) barrier protection against oropharyngeal pathogens via the activities of secretory immunoglobulin A and lactoferrin. Our pilot studies24, 25 established feasibility for this natural, easy, inexpensive intervention. Our data suggest that infants who receive this intervention may have enhanced immunocompetence and may reach full enteral feedings earlier,25 and that their mothers may have enhanced lactation and breastfeeding outcomes. Emerging data suggests additional benefits of oropharyngeal mother's milk, with and without buccal swabbing, including protection against blood-stream infection, ventilator-associated pneumonia, and necrotizing enterocolitis, earlier attainment of full enteral feeds (which can lead to a decreased length of hospitalization), enhanced maturation of oral feeding skills, improved growth, and enhanced breastfeeding outcomes.26-33 
Because it is an easy, natural, cost-effective intervention, oropharyngeal administration of own mother's colostrum and milk is quickly becoming standard care in NICUs through the United States. Some centers are providing the intervention every 2 hours for a 48-hour treatment period in the first days of life, while other centers are prolonging the duration of treatment from several days to several weeks. For the tiniest infants born as early as 23 weeks gestation, oropharyngeal administration of mother's milk may be given for a prolonged duration; up to 2 months, in order to mimic the effects of amniotic fluid exposure in the oropharynx, until per oral feedings are started at 32 weeks post-conceptional age. While these practices are quickly being incorporated into standard care, the delivery device and storage system for oropharyngeal administration of mother's colostrum/milk is not available. Because of this, clinicians (nurses and physicians) are utilizing a variety of different supplies (often unsterile) to administer the milk, and wide variation in the administration procedure itself may actually jeopardize patient safety.
The use of a cotton swab, dipped into a container of milk, prior to oropharyngeal administration, is common practice. This raises several concerns. First, the cotton fibers may become dislodged and aspirated during the (oropharyngeal administration of milk) procedure. If the cotton swab is completely saturated with milk, the entire (swab) head may become dislodged and aspirated; a medical emergency. While swabbing, the cotton swab creates friction to the fragile oral mucosa, that may result in breakdown and possible infection. Because the swab absorbs the majority (up to 97%) of the (milk) volume, the “dose” that is administered to the infant is widely variable, and inconsistent with subsequent doses. Finally, repeatedly dipping a cotton swab into a container of milk in preparation for each treatment may introduce pathogens into the milk and places the infant at risk for infection. Without an organized storage system, there is an increased likelihood that syringes (when prepared beforehand) may become contaminated or may not be used in the proper sequence. The present system allows for embodiments where the “doses” may be given in the same order that the milk was expressed, in order to maximize immune protection for the infant. An organized system allows for upright storage of syringes, in consecutive order so that the doses may be administered appropriately, and this system also permits nurses to easily find the next dose for more efficient use of time.
A standardized delivery device and storage system will enable clinicians to administer a precise “dose” of mother's colostrum and milk to the infant, using a standardized system to maintain sterility and promote patient safety. Because this treatment may be administered for a prolonged duration during the infant's hospitalization, a standardized delivery device and storage system is needed in order to ensure that all doses are administered as planned, and that infection-control practices are maintained. For example, for the smallest premature infants born at 23 weeks gestation, as many as 1008 doses (504 treatments; 2 syringes per treatment) may be administered during the infant's hospitalization. In some embodiments, the infant typically receives 24 treatments (of oropharyngeal colostrum) administered every 2 hours within the first 48 hours of life, which equals 48 doses since each treatment includes 2 syringes; one “dose” of milk for each cheek (i.e. one dose for the right buccal mucosa, and one for the left buccal mucosa). Thereafter, the infant may receive treatments every 3 hours (8 treatments per day; 2 doses per treatment) of oropharyngeal mother's milk daily, for a period of 9 weeks (63 days) until the infant reaches a post-conceptional age of 32 weeks; the earliest time when per oral feedings can be safely initiated for a preterm infant. If an infant is too clinically-unstable to begin per oral feeds at this time, the treatment period would be prolonged further and more doses would need to be prepared daily.
In some embodiments, fresh, never frozen, mother's milk may be used for this intervention in order to provide the infant with the highest concentration of (immune and trophic) protective biofactors. In the absence of fresh milk however, previously frozen mother's milk, and also donor breastmilk may be used. The use of fresh, never-frozen milk would enable the nurse to prepare several days worth of doses for oropharyngeal administration of mother's milk. For example, fresh milk can remain refrigerated for 48-72 hours, based on the hospital protocol. If not used within this period, it should be frozen so that it does not expire. Using the storage device disclosed herein, a nurse could prepare a total of 24 syringes for the infant, which would provide either 24 ‘single-syringe’ doses, or 12 ‘double-syringe’ doses. If an infant is receiving treatments every 2 hours (first 48 hours of life) the storage system can store enough “doses” for a 12 or a 24-hour treatment period. When the infant is receiving treatments every 3 hours, the storage system can store up to 3 days worth of “doses” when using a single-syringe system. The storage system disclosed herein reduces the risk for pathogen contamination during storage; decreasing infection risk for the infant.
The infants that would derive the most benefit from this intervention are very-low-birth-weight infants (VLBW: BW<1500 g) which account for 1.5% of all births in the United States; approximately 64,500 VLBW infants were born in 2007. On average, each VLBW infant would receive 392 treatments during hospitalization in the NICU, with calculations as follows; Initial treatment period: q 2 hour treatments×48 hours=24 treatments per subject, followed by the Extended treatment period: q 3 hour treatments×46 days on average (63 days for 23 wk infants, 28 days for 28 wk infants)=392 treatments; 784 doses per VLBW infant. This represents a total of 50,568,000 doses (syringes) for VLBW infants born in the United States annually. The delivery device and storage system of the present disclosure can be adapted for use with low birth weight (LBW: BW<2500 g) infants, which represent approximately 8.3% of all U.S. births annually and with any “at risk” term infant who is unable to breastfeed or feed ‘per oral’ from a bottle, as described below.